Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage‐specific trends in mycolic acid biosynthesis

MicrobiologyOpen

Damien Portevin⁶  Sudarkodi Sukumar⁵  Mireia Coscolla¹  Guanghou Shui³  Bowen Li⁴  Xue Li Guan¹  Anne K. Bendt²  Douglas Young⁶  Sebastien Gagneux¹ 

[1]Department of Medical Parasitology and Infection Biology, Swiss TPH, Basel, Switzerland

[2]Centre for Life Sciences, National University of Singapore, Singapore

[3]State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

[4]Department of Computer Science, National University of Singapore, Singapore

[5]Singapore-MIT Alliance, National University of Singapore, Singapore

[6]Mycobacterial Division Research, NIMR, MRC, London, United Kingdom

关键词: Genomics;    lipidomics;    mycolic acid;    phylogenetics;    tuberculosis;   

DOI  :  10.1002/mbo3.193

来源: Wiley

【 摘 要 】

Abstract

Mycolic acids (MAs) are α-alkyl, β-hydroxy long-chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti-tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages. We found significant variations in the MA patterns between different MTBC strains and lineages. MA patterns of “ancient” lineages contrasted those from “modern” lineages, with a lower representation of alpha-mycolates among Lineage 6 strains and an inversion of the methoxy: keto-mycolates ratio in Lineage 1 strains. By interrogating the whole genome sequences of these MTBC strains, we identified relevant single-nucleotide polymorphisms that may sustain the lineage-specific MA patterns. Our results show that the strain genetic background influences MA metabolism and suggests that strain diversity should be considered in the development of new anti-tuberculosis drugs that target MA synthesis.

【 授权许可】

CC BY   
© 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

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